Effect of Dapagliflozin on Inflammation and Endothelial Function

NCT02608905 | Terminated Phase 4 Results

• 1 other identifier: H-35985
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce hyperglycemia and improve peripheral insulin sensitivity by ameliorating glucotoxicity. Insulin resistance in type 2 diabetes (T2DM) is associated with endothelial dysfunction and vascular inflammation. Thus strategies to improve insulin sensitivity and lower glucotoxicity may improve endothelial inflammation and vascular inflammation. However, the effects of these agents on vascular inflammation and endothelial function is not known in patients with type 2 diabetes although anti-inflammatory properties have been demonstrated in various animal models. In the present study the investigators will assess if dapagliflozin treatment for 12 weeks decreases monocyte inflammation and improves endothelial function in patients with type 2 diabetes on metformin monotherapy.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)

  The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline in patients with type 2 diabetes.

  12 weeks

Secondary Outcomes (1)

• Arterial Flow Mediated Dilatation (%)

  12 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 5 mg daily by mouth for 2 weeks followed by 10 mg by mouth daily for 10 weeks

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Placebo tablets by mouth daily for 12 weeks

Drug: Placebo

Interventions

Dapagliflozin DRUG

Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.

Also known as: Farxiga

Dapagliflozin

Placebo DRUG

Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Men and women, ages 21 to 70 years. i) Women of childbearing potential must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
• ii) Women must not be pregnant or breastfeeding.
• Patients with Type 2 Diabetes Mellitus with the following parameters at study entry: hemoglobin A1c ranging from 7.0% to 9.0% and a fasting blood glucose less than or equal to 200 mg/dL.
• Patients must be on a stable dose of Metformin therapy for 3 months; the dose of metformin will not change for the duration of the study.
• Patients are allowed, but not required, to be on statins, Angiotensin Converting Enzyme (ACE) inhibitors, and angiotensin-receptor blockers at doses that have been stable for at least the last 3 months prior to enrollment in the study. Doses will not be changed for the duration of the study.
• Patients must have a Body Mass Index between 27-35 kg/m2
• Patients must have a stable body weight for three months prior to enrollment in the study.
• Patients must have a Creatinine Clearance greater than 60 mL/min (calculated by Cockcroft-Gault formula).
• Patients must have Hematocrit greater than or equal to 34%; Serum creatinine less than1.5 mg/dl in men and 1.4 mg/dl in women and Creatinine Clearance greater than 60 ml/min; and serum aspartate aminotransferase (AST) less than 2.5 times upper limit of normal, serum alanine transaminase (ALT) less than 2.5 times upper limit of normal, serum alkaline phosphatase less than 2.5 times upper limit of normal.

You may not qualify if:

• History of Type 1 diabetes mellitus
• Women who are pregnant or breastfeeding
• Patients receiving lipid-lowering medications other than statins within the last 3 months.
• Patient receiving SGLT-2 inhibitors, incretin therapy, dipeptidyl peptidase 4 (DPP-4) inhibitors, thiazolidinediones, insulin, sulfonylureas, alpha-glucosidase inhibitors, corticosteroids, immunosuppressive therapy, thiazide or loop diuretics, or hormone replacement therapy within the last 3 months .
• Patient must stop treatment with nonsteroidal anti-inflammatory drugs (NSAID) and antioxidant vitamin supplements at least one week prior to the start of the study
• Patients with diabetic gastroparesis.
• Patients with current tobacco use.
• Patients with active malignancy.
• Patients with history of urinary bladder cancer
• Patients with a history of clinically significant heart disease, peripheral vascular disease, or pulmonary disease will not be studied
• Subjects with a history of any serious hypersensitivity reaction to dapagliflozin.
• Prisoners, or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
• Patients with significant cardiac,hepatic or renal disease (Creatinine Clearance less than 60 mL/min calculated by Cockcroft-Gault formula) will be excluded.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Mandeep Bajaj
• Organization: Baylor College of Medicine

bajaj@bcm.edu

713-798-1712

Study Officials

• Mandeep Bajaj, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: November 20, 2015
• Study Start: November 1, 2015
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: April 8, 2020
• Results First Posted: April 8, 2020

Record last verified: 2020-04

Locations

US (1)